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Reinger, C.

Publications and source records attributed to Reinger, C..

3 recordsLinked to original sources

Genetic characterization of the apterous Life Span Enhancer in Drosophila melanogaster

The selector gene apterous (ap) of Drosophila melanogaster is best known for its prominent role in wing formation. apnull flies are viable but have no wings. However, apnull flies are associated with another phenotype whose analysis was largely neglected in the past 40 years: adults die precociously 2-3 days after eclosion. We have recently published a comprehensive analysis on the physiology of this striking phenotype. We showed that Ap protein is essential early in metamorphosis during hindgut remodeling where it is required for rectal papillae formation in the rectal ampulla. Wild-type flies have four rectal papillae that are involved in selective reabsorption of essential ions and metabolites from the primary urine produced by the Malpighian tubules. In apnull flies, rectal papillae formation is aborted prematurely. The corresponding papillar cells remain stuck in the rectal lumen. This leads to complete intestinal blockage and a cascade of pathologies resulting in premature death. In this study, we genetically identify and functionally dissect a novel tissue specific cis- regulatory element that directs Ap expression in the hindgut. This Life Span Enhancer (apLSE) maps to a [~]400 bp DNA fragment that is activated via only two small regulatory modules. Genetic analysis of apLSE alleles proves that they are essential for papilla formation and thus for adult survival. Our studies solve the 110-year-old enigma about the ap syndrome. They establish the apLSE as a key player linking hindgut morphogenesis and survival. We propose that several aspects of the ap syndrome are a consequence of drastic changes in endocrine homeostasis.

developmental biology↗

Intestinal control of feeding initiation in Drosophila melanogaster

The interplay between feeding and excretion is essential for organismal nutrition and survival, yet their mechanistic coupling remains poorly understood. At the onset of life, feeding must be initiated while developmental waste products - the meconium - need to be eliminated. Using Drosophila as a model system, we explored the in vivo mechanisms coordinating these processes. We developed novel behavioral assays for newly eclosed flies and discovered that, similar to neonatal mammals, Drosophila excrete their meconium shortly after eclosion. Remarkably, feeding initiation occurs only after partial meconium elimination. We identified a cis-regulatory element associated with the apterous gene, which, when disrupted, prevents both meconium excretion and adult feeding initiation. These flies develop hindgut obstruction (ileus), avoid food, and exhibit increased proboscis extension sleep - a behaviour we found plays a functional role in waste clearance under normal conditions. Through experimental inhibition of meconium excretion, we established that this process is prerequisite for feeding initiation, suggesting a gut-to-brain signaling circuit that couples these fundamental physiological processes. The progression of phenotypes we observed parallels the hallmarks of mechanical ileus in humans. Our findings reveal previously unrecognized links between intestinal clearance, feeding behavior, and survival, with potential implications for understanding similar processes across species.

developmental biology↗

Shaping and interpretation of Dpp morphogen gradient by endocytic trafficking

Dpp/BMP is a morphogen that controls patterning and growth in the Drosophila wing disc. Endocytic trafficking has been proposed to control extracellular Dpp spreading or removal, and Dpp signaling. However, how Dpp morphogen gradient is shaped and interpreted by endocytic trafficking remains unclear due to the lack of tools to visualize Dpp distribution at the physiological level. Here we generate functional fluorescent protein tagged dpp alleles to visualize both extracellular and intracellular Dpp distribution. Using these alleles, we found that, while Dynamin-mediated internalization of Dpp is required for Dpp signal activation, Rab5-mediated trafficking is not required for Dpp spreading or signaling as proposed before but for shutting off Dpp signaling through downregulating activated receptors. We provide evidence that Dpp signaling is terminated at Multivesicular body (MVB) likely through sorting activated receptors into intraluminal vesicles (ILVs) rather than Rab7-mediated lysosomal degradation. We further found that blocking MVB formation expanded Dpp signaling gradient without affecting extracellular Dpp gradient, thus compromising extracellular Dpp gradient interpretation. These results indicate that extracellular Dpp gradient is shaped by Dynamin-mediated internalization of Dpp and interpreted by duration of Dpp signaling.

developmental biology↗